Study to Compare Safety and Tolerability of AKST1210 Column at 2 Blood Flow Rates in Subjects With ESRD on Hemodialysis

NCT04985383 | Completed Results FDA Device

• 1 other identifier: AKST1210-101
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 4

Brief Summary

This study is to evaluate the safety and tolerability of the AKST1210 column at blood-flow rates greater than 250 mL/min in subjects with end-stage renal disease (ESRD) undergoing hemodialysis (HD). The study will assess the safety, tolerability, and impact on HD parameters when the AKST1210 column is used at a blood-flow of up to 450 mL/min.

Conditions

End-Stage Renal Disease

Outcome Measures

Primary Outcomes (4)

• Safety as Evaluated by Rate and Severity of Treatment-emergent AEs (TEAEs)

  A TEAE is defined as an AE that occurs on or after the date of the first column use. Primary and secondary endpoints were assessed at the beginning and end of each week of treatment for a particular column size and blood-flow rate combination (S-15 250 mL/min, S-15 up to 450 mL/min, S-25 250 mL/min, S-25 up to 450 mL/min, S-35 250 mL/min, S-35 up to 450 mL/min). The effect of blood-flow rate was assessed for a given column size as well as intra-subject and across-subject variability.

  Screening to Week 7

• Safety as Evaluated by the Number of Subjects With Intradialytic Hypotensive (IDH) Events

  The number and percentage of subjects with Intradialytic Hypotensive (IDH) event(s) summarized by column size and blood-flow rate combination. Primary and secondary endpoints were assessed at the beginning and end of each week of treatment for a particular column size and blood-flow rate combination (S-15 250 mL/min, S-15 up to 450 mL/min, S-25 250 mL/min, S-25 up to 450 mL/min, S-35 250 mL/min, S-35 up to 450 mL/min). The effect of blood-flow rate was assessed for a given column size as well as intra-subject and across-subject variability.

  Week 1 - S-15 at 250 mL/min, Week 2 - S-15 at up to 450 mL/min, Week 3 - S-25 at 250 mL/min, Week 4 - S-25 at up to 450 mL/min, Week 5 - S-35 at 250 mL/min, Week 6 - S-35 at up to 450 mL/min

• Safety as Evaluated by Changes in Total Hemoglobin (Hgb)

  Changes in post-HD total hemoglobin at baseline (i.e., the last non-missing value prior to the start of HD with the AKST1210 column) and each scheduled post-baseline timepoint summarized by each column size and blood-flow rate combination.

  Baseline, Week 1 - S-15 at 250 mL/min, Week 2 - S-15 at up to 450 mL/min, Week 5 - S-35 at 250 mL/min, Week 6 - S-35 at up to 450 mL/min

• Safety as Evaluated by Changes in Free Hemoglobin (Hgb)

  Changes in post-HD free hemoglobin at baseline (i.e., the last non-missing value prior to the start of HD with the AKST1210 column) and each scheduled post-baseline timepoint summarized by each column size and blood-flow rate combination.

  Baseline, Week 1 - S-15 at 250 mL/min, Week 2 - S-15 at up to 450 mL/min, Week 5 - S-35 at 250 mL/min, Week 6 - S-35 at up to 450 mL/min

Secondary Outcomes (9)

• Adequacy of Hemodialysis Measured With Kt/V

  Week 1 - S-15 at 250 mL/min, Week 2 - S-15 at up to 450 mL/min, Week 3 - S-25 at 250 mL/min, Week 4 - S-25 at up to 450 mL/min, Week 5 - S-35 at 250 mL/min, Week 6 - S-35 at up to 450 mL/min

• Adequacy of Hemodialysis Measured by Urea Reduction Ratio (URR)

  Week 1 - S-15 at 250 mL/min, Week 2 - S-15 at up to 450 mL/min, Week 3 - S-25 at 250 mL/min, Week 4 - S-25 at up to 450 mL/min, Week 5 - S-35 at 250 mL/min, Week 6 - S-35 at up to 450 mL/min

• Total Fluid Balance for Each Column-Size Blood-Flow Rate Combination

  Week 1 - S-15 at 250 mL/min, Week 2 - S-15 at up to 450 mL/min, Week 3 - S-25 at 250 mL/min, Week 4 - S-25 at up to 450 mL/min, Week 5 - S-35 at 250 mL/min, Week 6 - S-35 at up to 450 mL/min

• Number of Participants Who Achieved the Dry Weight Goal

  Week 1 - S-15 at 250 mL/min, Week 2 - S-15 at up to 450 mL/min, Week 3 - S-25 at 250 mL/min, Week 4 - S-25 at up to 450 mL/min, Week 5 - S-35 at 250 mL/min, Week 6 - S-35 at up to 450 mL/min

• Plasma Beta-2 Microglobulin (b2M) Concentrations (Before and After HD) and Contribution of the AKST1210 Column to b2M Removal at Each Column Size and Blood-flow Rate

  Week 1 (V7) - S-15 at 250 mL/min, Week 2 (V10) - S-15 at up to 450 mL/min, Week 3 (V13) - S-25 at 250 mL/min, Week 4 (V16) - S-25 at up to 450 mL/min, Week 5 (V19) - S-35 at 250 mL/min, Week 6 (V22) - S-35 at up to 450 mL/min

Study Arms (1)

AKST1210 device

EXPERIMENTAL

AKST1210 column will be connected in series for the duration of each hemodialysis session.

Device: AKST1210 S-15 at 250 mL/min; Device: AKST1210 S-15 at 450 mL/min; Device: AKST1210 S-25 at 250 mL/min; Device: AKST1210 S-25 at 450 mL/min; Device: AKST1210 S-35 at 250 mL/min; Device: AKST1210 S-35 at 450 mL/min

Interventions

AKST1210 S-15 at 250 mL/min DEVICE

Procedure: Hemodialysis, AKST1210 column size 150mL and blood-flow rate at 250mL/min

Also known as: S-15 at 250 mL/min

AKST1210 device

AKST1210 S-15 at 450 mL/min DEVICE

Procedure: Hemodialysis, AKST1210 column size 150mL and blood-flow rate at 450mL/min

Also known as: S-15 up to 450 mL/min

AKST1210 device

AKST1210 S-25 at 250 mL/min DEVICE

Procedure: Hemodialysis, AKST1210 column size 250mL and blood-flow rate at 250mL/min

Also known as: S-25 at 250 mL/min

AKST1210 device

AKST1210 S-25 at 450 mL/min DEVICE

Procedure: Hemodialysis, AKST1210 column size 250mL and blood-flow rate at 450mL/min

Also known as: S-25 at 450 mL/min

AKST1210 device

AKST1210 S-35 at 250 mL/min DEVICE

Procedure: Hemodialysis, AKST1210 column size 350mL and blood-flow rate at 250mL/min

Also known as: S-35 at 250 mL/min

AKST1210 device

AKST1210 S-35 at 450 mL/min DEVICE

Procedure: Hemodialysis, AKST1210 column size 350mL and blood-flow rate at 450mL/min

Also known as: S-35 at 450 mL/min

AKST1210 device

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females aged 40 - 75 years, inclusive.
• End Stage Renal Disease (ESRD) requiring HD.
• Dialysis vintage ≥ 24 months.
• Absence of clinically-relevant residual renal function.
• Regular Hemodialysis (HD) sessions done at blood-flow rates between 400 and 500 mL/min, and with inter-dialysis intervals of 48 hours or more.
• Stable health status for at least 4 weeks prior to screening based on medical history, and findings from physical examination, laboratory tests, vital signs, and ECG, as assessed by the investigator.
• Life expectancy \> 6 months (as determined by the investigator).
• Body mass index (BMI) between 18 and 37 kg/m2, inclusive, with a minimum body weight of 52 kg.
• Must be on stable doses (\> 4 weeks) of all treatments for concomitant diseases (e.g., diabetes, hypertension), but this does not apply to medications for conditions related to ESRD (e.g., medications for calcium and phosphate control, anemia).
• Must be able to follow the study protocol and receive the treatment in the established timeframe.
• Must provide a signed and dated informed consent form.

You may not qualify if:

• Patients for whom adequate anticoagulation cannot be achieved, such as those with severe anemia, severe hemorrhagic diathesis, severe gastrointestinal ulcers, or who are receiving anticoagulant medications for any reason other than as required for HD. Use of antiplatelet drugs (e.g., aspirin or clopidogrel) is allowed.
• Patients for whom extracorporeal circulation therapy is contraindicated, such as those with severe cardiac insufficiency, acute myocardial infarction, severe cardiac arrhythmia, acute seizure disorder, or severe uncontrolled hypertension.
• Patients with Kt/V \< 1.2 during recent 8-week period prior to run-in.
• History of hypersensitivity to heparin, including heparin-induced thrombocytopenia.
• History of hypersensitivity to the AKST1210 column or its components.
• Patients who are not anticipated to be able to tolerate blood-flow rates of 450 mL/min during HD (e.g., new vascular access that cannot be used with 14G or 15G needles).
• Patients who are at higher risk for intradialytic hypotension (IDH) including:
• Medical records indicating the occurrence IDH (SBP \< 90 mmHg) in more than 30% of HD sessions during a recent 8-week period prior to run-in;
• Patients requiring or expected to require extensive fluid management as determined by the investigator;
• Presence of pre-dialysis hypotension, defined as SBP \< 90 mmHg and/or diastolic blood pressure (DBP) \< 50 mmHg, before any of the last 3 dialysis sessions prior to screening;
• Diagnosis of IDH in medical records;
• Diagnosis of autonomic dysfunction;
• Patients who frequently require a ultrafiltration rate (UFR) above 13 mL/kg/h.
• Patients who are pregnant or breast-feeding or who are planning to become pregnant. Female subjects must not be pregnant or breastfeeding. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at screening and prior to start of treatment. WOCBP and men must agree to use highly-effective contraception (Clinical Trial Facilitation Group 2014) prior to study entry. A woman is considered of childbearing potential following menarche and until becoming postmenopausal (no menses for at least 2 years without an alternative cause). Should a woman become pregnant or suspect she is pregnant while she or her male partner is participating in the study, she should inform her treating physician immediately.
• Clotting disorders.

Sponsors & Collaborators

• Alkahest, Inc.: lead

Study Sites (4)

Renal Consultant Medical Group

Granada Hills, California, 91344, United States

Location

Valley Renal Medical Group Research

Northridge, California, 91324, United States

Location

US Renal Care

Gallup, New Mexico, 87301, United States

Location

US Renal Care - Westover Hills Dialysis

San Antonio, Texas, 78251, United States

Location

MeSH Terms

Conditions

Kidney Failure, Chronic

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

After the study was closed, unreliable data was identified at a single study site and has not been presented here.

Results Point of Contact

• Title: Head of Communications
• Organization: Alkahest, Inc.

sm-Trials-alkahest@grifols.com

(650) 801-0474

Study Officials

• Alkahest Medical Monitor

  Alkahest, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2021
• First Posted: August 2, 2021
• Study Start: March 11, 2021
• Primary Completion: September 1, 2021
• Study Completion: September 1, 2021
• Last Updated: September 29, 2023
• Results First Posted: September 29, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)